Abstract
Ever since biologics were introduced in the treatment of RA around 10 years ago, concerns about their safety profiles, including cancer, have been raised. In the case of cancer, these concerns are based on our incomplete understanding of the full effects of these drugs, or the pathways that they inhibit, and their relation to cancer. Thus, it has been difficult to formulate specific hypotheses regarding what to expect (Which cancer types? In which patients? When?), and it will take time until we feel confident that all relevant risks are well characterized. Through RCT meta-analyses and observational studies including the biologics registers, some data have emerged. So far, but with exceptions both in terms of risks observed and absence of data, the emerging picture is reassuring rather than alarming.
Zusammenfassung
Seit Einführung von Biologika in die Therapie der rheumatoiden Arthritis vor etwa 10 Jahren sind Bedenken hinsichtlich ihres Sicherheitsprofils, einschließlich Malignomen, erhoben worden. Dabei basieren diese Bedenken auf dem unvollständigen Verständnis der gesamten Wirkungen dieser Präparate bzw. der Signalwege, die sie hemmen, und ihrer Beziehung zu Malignomen. Folglich ist es schwierig, bestimmte Hypothesen im Hinblick auf das zu formulieren, was zu erwarten ist (Welche Krebsarten? Bei welchen Patienten? Wann?), und es braucht Zeit, bis wir überzeugt sind, dass alle relevanten Risiken ausreichend beschrieben wurden. Einige Daten konnten durch Metaanalysen von randomisierten kontrollierten Studien und Beobachtungsstudien einschließlich der Biologika-Register schon erhoben werden. Bisher ist das sich abzeichnende Bild eher ermutigend als alarmierend, mit Ausnahmen hinsichtlich beobachteter Risiken und fehlender Daten.
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References
Smitten AL, Simon TA, Hochberg MC, Suissa S (2008) A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther 10(2):R45
Baecklund E, Iliadou A, Askling J et al (2006) Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54(3):692–701
Hellgren K, Smedby KE, Feltelius N et al (2010) Do rheumatoid arthritis and lymphoma share risk factors? A comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis. Arthritis Rheum 62(5):1252–1258
Balkwill F (2006) TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev 25(3):409–416
Askling JF, Nordstrom K, Ross B et al (2010) Cancer risk with tumour necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. DOI: 10.1002/art.24941
Bongartz T, Sutton AJ, Sweeting MJ et al (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285
Bongartz T, Warren FC, Mines D et al (2009) Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials. Ann Rheum Dis 68(7):1177–1183
Leombruno JP, Einarson TR, Keystone EC (2009) The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events. Ann Rheum Dis 68(7):1136–1145
Lunt M, Watson KD, Dixon WG et al (2010) No evidence of association between anti-TNF treatment and mortality in patients with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. DOI 10.1002/art.27660
Strangfeld A, Hierse F, Rau R et al (2010) Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther 12(1):R5
Askling J, Vollenhoven RF van, Granath F et al (2009) Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment? Arthritis Rheum 60(11):3180–3189
Wolfe F, Michaud K (2007) Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 56(9):2886–2895
Setoguchi S, Solomon DH, Weinblatt ME et al (2006) Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum 54(9):2757–2764
Askling J, Baecklund E, Granath F et al (2009) Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register. Ann Rheum Dis 68(5):648–653
Wolfe F, Michaud K (2007) The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person–years of observation. Arthritis Rheum 56(5):1433–1439
Mariette X, Tubach F, Bagheri H et al (2010) Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry. Ann Rheum Dis 69(2):400–408
Askling J (2009) group As. ANTI-TNF therapy and risk of skin cancer, data from the Swedish artis registry 1998–2006. EULAR 2009
Franklin J, Lunt M, Bunn D et al (2007) Influence of inflammatory polyarthritis on cancer incidence and survival: results from a community-based prospective study. Arthritis Rheum 56(3):790–798
Raaschou P, Askling J, group tAs (2008) Are cancer occurring against a background of anti-TNF particularly aggressive? ACR 2008
Dixon WG, Watson KD, Lunt M et al (2010) Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken) 62(6):755–763
Rennard SI, Fogarty C, Kelsen S et al (2007) The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175(9):926–934
Simard J, Neovius M, Hagelberg S, Askling J (2010) Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study. Arthritis Rheum. DOI: 10.1002/art.27741
Conflict of interest
Johan Askling has received speaker’s honorarium (<2000USD) from Wyeth/Pfizer and BMS. He has been involved in studies based on data from the Swedish Biologics Register. This register has received funding from BMS, Wyeth/Pfizer, Merck, Abbott, Roche and Biovitrum.
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Askling, J. The risk of malignancies in RA patients treated with biologics. Z. Rheumatol. 69, 774–779 (2010). https://doi.org/10.1007/s00393-010-0639-8
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DOI: https://doi.org/10.1007/s00393-010-0639-8